Circulating endothelial cells in patients with chronic lymphocytic leukemia

作者：Gian Matteo Rigolin, Rossana Maffei, Lara Rizzotto, Maria Ciccone, Olga Sofritti, Giulia Daghia, Francesca Cibien, Francesco Cavazzini, Roberto Marasca, Antonio Cuneo · 发表于：Cancer · 年份：2010 · DOI：10.1002/cncr.24961 · 被引用次数：37 · 研究领域：Angiogenesis and VEGF in Cancer、Lymphatic System and Diseases、Chronic Lymphocytic Leukemia Research

BACKGROUND: In patients with cancer, circulating endothelial cells (CECs) are increased and are correlated with an aggressive disease course. However, the clinical and biologic significance of CECs in chronic lymphocytic leukemia (CLL) remains uncertain. METHODS: In 170 patients with CLL, CEC levels were quantified by flow cytometry and were correlated with clinical and biologic data. In addition, CECs were characterized by immunophenotypic, fluorescence in situ hybridization (FISH), and gene expression profile analyses. RESULTS: In patients with CLL, CECs were increased compared with controls. A higher level of CECs (>20/microL) identified a subset of patients with a more aggressive disease course characterized by a shorter time to first treatment both in univariate and multivariate analyses. In FISH analysis, 7 patients had a significant proportion of CECs and presented with the same cytogenetic lesion of neoplastic lymphocytes and immunophenotypic features of endothelial progenitor cells. The gene expression profile of sorted CECs revealed a molecular pattern, suggesting a derivation from CLL leukemic cells with increased cell survival and proliferation, diminished cell adhesion to extracellular matrix, and enhanced proangiogenic function compared with their normal counterparts. CONCLUSIONS: The current data suggest that, in CLL, CECs may represent a biologic marker of aggressiveness and disease progression to be considered for new, targeted antiangiogenic treatments.